Understanding Medication Discontinuation in Depression

Understanding Medication Discontinuation in Depression

Compared with schizophrenia, adherence behavior has been relatively overlooked in depression and other mood disorders.1-3 Major depression is increasingly thought of as a chronic illness.4 In most chronic illnesses, ideal concordance is the exception, not the rule. Barber and colleagues5 found that only 16% of patients taking medication for stroke, coronary heart disease, asthma, diabetes mellitus, and rheumatoid arthritis were adherent, problem-free, and in receipt of sufficient information when examined at 10 days. Should we expect our patients with mental health problems to be more or less able to adhere to our recommendations? Furthermore, are we more or less willing than our colleagues in other medical specialties to take the time to promote problem-free adherence in our patients?

Three new studies suggest that physicians should be vigilant for adherence difficulties in patients with depression (Table 1). In the Medical Expenditure Panel Survey, Olfson and colleagues6 looked at 829 people who had started antidepressant treatment for depression. Their findings showed that 42% discontinued antidepressants during the first 30 days and 72% had stopped within 90 days. Bambauer and colleagues7 documented partial nonadherence in 75% of individuals who were depressed, culminating in an average of 40% of days without taking dispensed antidepressants.

Types of poor medication adherence
Type 1. Full discontinuation   Stopping a prescribed course of medication against
medical advice (or in the absence of medical advice)
Type 2. Partial nonadherence   Interrupting a prescribed course of medication against
medical advice (or in the absence of medical advice)
Type 3. Suboptimal dosing   Taking too much or, more commonly, too little medication;
concordance with 80% of prescribed doses may be used
as a threshold for poor vs adequate compliance

A prospective cohort study from Amsterdam used 6-month follow-up of 147 primary care patients who had been given a new prescription for a nontricyclic antidepressant.8 Adherence behavior was closely monitored using an electronic pill container over a total of more than 20,000 patient-days. In this sample, the mean number of correct medication intakes was 74%, with 69% of the patients exhibiting adequate adherence (taking more than 80% of medication doses). Remarkably, only 3% followed the medication regimen exactly as prescribed.

These findings are in line with those of previous studies. In a sample of 272 patients with major depression treated by 91 primary care physicians, 48% had dropped out of treatment by week 12.9 In a large study of 240,604 patients who were given a new antidepressant prescription, 70% discontinued within 6 months.10 Recently analyzed adherence data from a study of more than 740,000 patients in whom treatment with an SSRI was newly started showed that almost half the patients failed to adhere to therapy for 60 days or more, and only 28% were compliant at 6 months.11 Even in tightly controlled trial environments, discontinuation rates for SSRIs have typically been above 70%.12

One important question concerns whether the choice of drug has any effect on adherence. Head-to-head studies of discontinuation rates have yet to be properly compiled, but work to date hints that discontinuation rates with tricyclics are only marginally worse than with newer antidepressants.13-16 Physicians must decide whether this is clinically significant in conjunction with other factors. Yet even within a drug class there may be subtle differences in adherence between those taking different SSRIs, according to new data from 116,090 patients in the Integrated Healthcare Information Services National Managed Care Database who had started treatment with an SSRI.17

What factors can explain these high discontinuation rates and even higher rates of missed medication doses? Evidence is slowly emerging that preexisting treatment preferences, trust in medication and the prescriber, and treatment-emergent problems are more important than severity of depression or loss of insight (Table 2). In fact, given the information available to that individual, most cases of discontinuation appear to be intentional and rational.

Summary of predictors of
missed antidepressant medication
External factors   Lack of support
Interruption of supply
Patient (intentional)   Concerns about medication/stigma
Concerns about cost
Lack of efficacy
Patient (nonintentional)   Cognitive impairment
Complexity of regimen
Loss of insight
Misunderstanding instructions
Previous negative experience
Health care professional–related factors   Poor therapeutic alliance
Poor empathy
Little explanation about medication
Inadequate follow-up


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